Secretory IgA antibodies play a key role in immunologic defense of mucosal surfaces; they are most efficiently stimulated by mucosally applied antigen. However, many antigens are rather inefficient mucosal immunogens. The prospects for effective mucosal immunization with nonliving antigens should be much improved if simple methods for enhancing mucosal secretory IgA responses by the use of adjuvants were available. The major goals of the proposed studies are to identify materials that act as adjuvants for mucosal secretory IgA responses, to determine how they can be used most efficiently, and to study selected aspects of adjuvant induced secretory IgA responses in experimental animals. The methods will involve precise quantitative assessment in rats of the effects of adjuvants on directly measured mucosal secretory IgA responses to several antigens of V. cholerae (cholera toxin or heat aggregated toxin, LPS, and whole killed bacteria) given enterically. Materials to be studied for adjuvant effects include: lipid A, LPS, and whole bacteria (of E. coli and V. cholerae), MDP derivatives, CP-20961, poly I:C, poly A:U, and others. Our specific aims are to, 1) identify and quantitatively compare materials which have adjuvant activity when mixed with a mucosally applied antigen, 2) determine whether conjugation of antigen to adjuvant enhances the adjuvant effect, 3) evaluate liposomes as effective carriers for mucosally applied antigens and adjuvants, 4) compare adjuvant effects on primary and secondary mucosal secretory IgA responses, 5) determine whether adjuvants enhance mucosal secretory IgA responses or promote altered forms of response, i.e. tolerance, in immature or protein-deprived rats, and 6) develop immunization regimens which can be used to test the efficacy of mucosal adjuvants in immunization against a specific mucosal infection: experimental cholera. The results of these studies should directly aid efforts to develop effective topical vaccines for cholera, related enteric infections, and variety of infections that involve other mucosal surfaces, e.g. the respiratory tract, urogenital tract, and conjunctivae. They should also aid efforts to protect suckling infants by mucosal immunization of mothers leading to secretory IgA responses in breast milk.